Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group.

PURPOSE The importance of the timing of thoracic irradiation (TI) in the combined modality therapy of limited-stage small-cell lung cancer (SCLC) was assessed in a randomized trial. METHODS All 308 eligible patients received cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each chemotherapy regimen. Patients randomized to early TI received 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP (week 3), and late TI patients received the same radiation concurrent with the last cycle of EP (week 15). After completion of all chemotherapy and TI, patients without progressive disease received prophylactic cranial irradiation (25 Gy in 10 fractions over 2 weeks). RESULTS Although complete remission rates were not significantly different between the two arms, progression-free survival (P = .036) and overall survival (P = .008) were superior in the early TI arm. Patients in the late TI arm had a higher risk of brain metastases (P = .006). CONCLUSION The early administration of TI in the combined modality therapy of limited-stage SCLC is superior to late or consolidative TI.